This proposal originally encompassed 3 discrete projects comprised of the following items: clinical/pharmacologic studies of all- trans retinoic acid (RA) in acute promyelocytic leukemia (APL) to include an evaluation of mechanisms and means of overcoming acquired clinical resistance; 2) use of a newly developed polymerase chain reaction assay for the molecular marker of APL (fusion of the retinoic acid receptor-alpha with the PML gene) as a means of detecting and monitoring disease activity during complete remission (CR); and 3) use of anti-CD33 monoclonal antibodies as a means of eradicating minimal residual disease after CR. The monoclonal antibody project was eliminated in peer review by the study section, and the tentative award for the remaining two-thirds of the application was administratively reduced by 50%, leaving sufficient funds for one-third of the original project. Based on the study section critique, only project #1 (clinical pharmacology) will be conducted under this grant.